AKR1C3 metabolizes various androgen metabolites including 5a-dihydrotestosterone to 5a-androstane-3a,17b-diol, Delta4-androstene-3,17-dione to testosterone, androstanedione to 5a-dihydrotestosterone, androsterone to 5a-androstane-3a,17b-diol. AKR1C3 is also involved in estrogen metabolism converting estrone to 17b-estradiol as well as progesterone metabolism converting prostaglandin D2 to 9a,11b-prostaglandin F2a. AKR1C3 has the capability of regulating the trans-activation of various nuclear receptors including androgen receptor, estrogen receptor, and peroxisome proliferator activated receptor (PPARG) by regulating the ligand availability for the nuclear receptors.

Homology

A member of the of AKR1C family proteins; AKR1C1, AKR1C2, AKR1C3, AKR1C4 in human, and AKR1C9 in rat.

Expression of AKR1C3 mRNA was reduced in breast tumor as compared to adjacent normal breast tissue. Immunohistochemstry revealed that the ductal epithelial cells and stromal cells of the breast express AKR1C3. In myoepithelial cells of the breast, immunoreactive AKR1C3 was absent in normal tissues, whereas strong AKR1C3 staining was apparent in cells surrounding the neoplastic epithelium of ductal carcinoma in situ.

The aldo-keto reductase AKR1C3 is a novel suppressor of cell differentiation that provides a plausible target for the non-cyclooxygenase-dependent antineoplastic actions of nonsteroidal anti-inflammatory drugs.